These observations are in good agreement with data reported by Depasquale and Thompson [6] which demonstrated that PAR-1 expression is a negative prognostic factor in melanomas and strongly correlates with tumor stage. Patients with B-CLL, in most cases, have an indolent clinical course which is asymptomatic and requires no treatment [19]. On the other hand, B-ALL is believed to derive from blockade in maturation of bone marrow lymphoid progenitors leading to bone marrow infiltration, occurrence of various cytopenias in peripheral blood and appearance of blast cells with high proliferative ability. Therefore, patients with B-ALL show
a more aggressive clinical BTK inhibitor research buy behavior than patients with B-CLL [20]. In this study we observed that patients with B-CLL showed similar PAR-1 expression levels in comparison to lymphocytes from healthy individuals. On the other hand, patients with B-ALL exhibited, on average, a significant increase in the expression of this receptor when compared to normal lymphocytes. Interestingly, patients classified as at high risk showed the highest PAR-1 levels among B-ALL patients. CML is a myeloproliferative disease which is characterized by the presence of the fusion gene BCR-ABL, an oncoprotein generated by reciprocal translocation between chromosomes 9 and 22, t(9;22) [21]. In this study,
flow cytometric analyses demonstrated that CML patients in the chronic phase (CML-CP) exhibited a significant decrease in PAR-1 when compared to
granulocytes from healthy individuals. Since PAR-1 has been implicated in inflammatory GSK269962 clinical trial responses as well as in innate and adaptive immunity [22], it is possible PLEK2 that down-regulation of this receptor may contribute for reduced function of these cells and increased susceptibility to recurrent infections in CML. Progression of CML-CP to CML-BP is not fully understood. In fact it is believed that BCR-ABL in cooperation with other factors may account for accelerated leukemogenesis and drug resistance in the acute phase [21]. In this study, we identified an increased PAR-1 expression in blasts from CML-BP patients. However, it is clear that a more extensive analysis is needed to determine the biological significance of these results. Acute myelomonocytic leukemia, which comprises subtypes M4 and M5, are highly aggressive and have a median survival time of only 12 months [23]. Samples from AML-M4/M5 patients that were analyzed in this study exhibited high levels of PAR-1 receptor when compared to monocytes and granulocytes from healthy donors. In contrast, patients with AML-M3 showed PAR-1 expression levels that were similar to those found in granulocytes from healthy donors. However, 3 out of 10 patients exhibited high levels of this receptor.